Prone Individuals Research Articles

Infantile Epileptic Encephalopathy with Hypsarrhythmia (Infantile Spasms/West Syndrome) and Immunity

West syndrome is a severe epilepsy, occurring in infancy, that comprises epileptic seizures known as spasms, in clusters, and a unique EEG pattern, hypsarrhythmia, with psychomotor regression. Maturation of the brain is a crucial component. The onset is within the first year of life, before 12 months of age. Patients are classified as cryptogenic (10 to 20%), when there are no known or diagnosed previous cerebral insults, and symptomatic (80 to 90%), when associated with pre-existing cerebral damages. The time interval from a brain insult to infantile spasms onset ranged from 6 weeks to 11 months. West syndrome has a time-limited natural evolutive course, usually disappearing by 3 or 4 years of age. In 62% of patients, there are transitions to another age-related epileptic encephalopathies, the Lennox-Gastaut Syndrome and severe epilepsy with multiple independent foci. Spontaneous remission and remission after viral infections may occur. Therapy with ACTH and corticosteroids are the most effective. Reports about intravenous immunoglobulins action deserve attention. There is also immune dysfunction, characterized mainly by anergy, impaired cell-mediated immunity, presence of immature thymocytes in peripheral blood, functional impairment of T lymphocytes induced by plasma inhibitory factors, and altered levels of immunoglobulins. Changes in B lymphocytes frequencies and increased levels of activated B cells have been reported. Sensitized lymphocytes to brain extract were also described. Infectious diseases are frequent and may, sometimes, cause fatal outcomes. Increase of pro-inflamatory cytokines in serum and cerebrospinal fluid of epileptic patients were reported. Association with specific HLA antigens was described by several authors (HLA-DR7, HLA-A7, HLA-DRw52, and HLA-DR5). Auto-antibodies to brain antigens, of several natures (N-methyl-d-aspartate glutamate receptor, gangliosides, brain tissue extract, synaptic membrane, and others), were described in epileptic patients and in epileptic syndromes. Experimental epilepsy studies with anti-brain antibodies demonstrated that epileptiform discharges can be obtained, producing hyperexcitability leading to epilepsy. We speculate that in genetically prone individuals, previous cerebral lesions may sensitize immune system and trigger an autoimmune disease. Antibody to brain antigens may be responsible for impairment of T cell function, due to plasma inhibitory effect and also cause epilepsy in immature brains. Keywords: West syndrome, Lennox-Gastaut syndrome, multifocal independent spikes, autoimmunity, cell-mediated immunity, humoral immunity

A new value of proximal femur geometry to evaluate hip fracture risk: True moment arm

This study was undertaken to determine the influence of proximal femur geometry on hip fracture risk independent of bone mineral density. We examined 34 hip fracture subjects (17 men, 17 women) and 36 control subjects (18 men, 18 women). The control subjects were matched with the hip fracture patients by femoral neck bone mineral density (+ or - 0.100 g/cm(2)). Hip axis length (HAL), femoral axis length (FAL), femoral neck-shaft angle (Theta angle), lateral and medial femoral cortical thickness were measured on standart pelvic radiographs. In the literature, there are conflicting views of the relationship between femur geometry and hip fracture risk which may be explained by different definitions of some parameters. We investigated the effect of a new parameter called true moment arm (TMA) on hip fracture risk. Longer TMA may be correlated to higher transmission of impact energy to the femoral neck. Thus it may be useful to define fracture prone individuals. The results of this study showed that HAL, FAL and TMA were significantly longer in the hip fracture subjects compared to the control group (p<0.001). Hip fracture patients had thinner lateral and medial femoral cortical thickness (p<0.001). Theta angle was wider in the hip fracture group than in the control group (p<0.001). In conclusion, our study showed that evaluation of TMA in addition to HAL, FAL, Theta angle, MCT and LCT can be used to determine of the fracture risk independently of BMD.

Central role of dendritic cells in the regulation and deregulation of immune responses.

Dendritic cells (DCs) play a critical role in orchestrating the innate and adaptive components of the immune system so that appropriate, coordinated responses are mounted against infectious agents. Tissue-resident DCs interact with microbes through germline-encoded pattern-recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms. Antigens use PRR activation to instruct DCs for the appropriate priming of natural killer (NK) cells, followed by specific T-cell responses. Due to the central role of DCs in regulating the activation and progression of immune responses, minor imbalances in the feedback control of Toll-like receptor (TLR)-activated cells have been associated with autoimmunity in genetically prone individuals. We review here recent findings on the role of DCs in the priming of innate and adaptive immune responses and the possible involvement of DCs in inducing and maintaining autoimmune reactions.

Reasoning and Delusion Proneness

The present study was an investigation into the reasoning of delusion prone individuals. Seventy healthy individuals in the general population completed a measure of delusion proneness and engaged in 8 trials of difficult probabilistic reasoning tasks, 4 emotionally neutral and 4 emotionally salient, and were asked to report their level of confidence in their decisions. While delusion prone individuals did not request any fewer stimuli on reasoning tasks than did individuals who were not delusion prone, delusion prone individuals were more confident in their decisions on the neutral task than individuals who were not delusion prone and were more confident in their decision on the first trial, regardless of the type of stimuli presented. Further, despite requesting less information on neutral than salient tasks, delusion prone individuals reported equivalent confidence on both tasks. Delusion proneness and delusion onset may be related to overconfidence in decisions, particularly overconfidence in initial judgment.

A new value of proximal femur geometry to evaluate hip fracture risk: true moment arm

This study was undertaken to determine the influence of proximal femur geometry on hip fracture risk independent of bone mineral density. We examined 34 hip fracture subjects (17 men, 17 women) and 36 control subjects (18 men, 18 women). The control subjects were matched with the hip fracture patients by femoral neck bone mineral density (+ or - 0.100 g/cm(2)). Hip axis length (HAL), femoral axis length (FAL), femoral neck-shaft angle (Theta angle), lateral and medial femoral cortical thickness were measured on standart pelvic radiographs. In the literature, there are conflicting views of the relationship between femur geometry and hip fracture risk which may be explained by different definitions of some parameters. We investigated the effect of a new parameter called true moment arm (TMA) on hip fracture risk. Longer TMA may be correlated to higher transmission of impact energy to the femoral neck. Thus it may be useful to define fracture prone individuals. The results of this study showed that HAL, FAL and TMA were significantly longer in the hip fracture subjects compared to the control group (p<0.001). Hip fracture patients had thinner lateral and medial femoral cortical thickness (p<0.001). Theta angle was wider in the hip fracture group than in the control group (p<0.001). In conclusion, our study showed that evaluation of TMA in addition to HAL, FAL, Theta angle, MCT and LCT can be used to determine of the fracture risk independently of BMD.

Role of Toll like receptor-activated dendritic cells in the development of autoimmunity

The recognition of microbial stimuli by Toll-like receptors (TLRs) expressed on dendritic cells (DCs) is essential for the regulation of immune responses. DC activation via TLRs leads to the production of proinflammatory cytokines, chemokines and surface molecules that play a key role in the regulation and control of inflammatory reactions and adaptive immunity. Minor imbalances in the feedback control of TLR-activated innate immune cells have been associated with autoimmunity in genetically prone individuals. We review here recent studies indicating how TLR-mediated activation of innate immune cells, including DCs, may be involved in the development and/or maintenance of autoimmune responses in the presence of both endogenous and exogenous ligands.

Role of Hereditary Factors in Weight Loss and Its Maintenance

The prevalence of obesity is increasing worldwide at an alarming rate in both developed and developing countries. Obesity is a chronic complex disease of multifactorial origin resulting from a long-term positive energy balance, in which both genetic and environmental factors are involved. Genetically prone individuals are the first to accumulate fat in the present obesogenic environment. Obesity increases the risks of type 2 diabetes, hypertension, cardiovascular disease, dyslipidemia, arthritis, and several cancers and reduces the average life expectancy. Implementation of effective strategies in prevention and management of obesity should become an important target in health care systems. Weight changes throughout life depend on the interaction of behavioral, genetic and environmental factors. Weight loss in response to weight management shows a wide range of interindividual variation which is largely influenced by genetic determinants. The strong control of weight loss by genotype was confirmed by twin and family studies. Recently, special attention has been paid to nutritional, hormonal, psychobehavioral and genetic factors which can predict the response to weight reduction programme. In this article currently available data on the role of obesity candidate gene polymorphisms in weight loss and maintenance are reviewed. It is believed that an elucidation of the genetic component in the prognosis of weight management could assist in the development of more effective and individually tailored therapeutic strategies.

Let’s stick together

If there is one defining characteristic of a melanocyte it is the melanosome, the organelle dedicated to the synthesis and containment of melanin. Once a melanosome is made, the question is what happens next. For neural crest-derived melanocytes, as opposed to the retinal pigment epithelium, the ultimate destination of melanosomes is likely to be surrounding keratinocytes where they will function to prevent UV-induced DNA damage. Over the years, a lot has been discovered about the process of melanosome genesis and the enzymes involved in the manufacture of pigment. More recently the molecular mechanisms that direct melansomes to the cell periphery and along their dendritic processes have been deciphered, though there is still much to learn. Yet remarkably, the final step in the journey, how melanosomes are transferred to keratinocytes and what happens once transfer has taken place remains a mystery. Despite the efforts of several laboratories, no clear underlying mechanism has been described. What is clear though is that in the natural context in the skin, intimate contact between the melanocyte and surrounding keratinocytes is likely to be critical. In this issue the paper from Joshi et al., reveals a feature of the consequences of melanosome transfer to keratinocytes; the release of calcium from an intracellular source within the keratinocyte. The results further suggest that there are specific melanocyte membrane-associated proteins that are necessary for the Ca2+ signal. The paper is interesting in that it raises several interesting questions. First, what is the source of the intracellular calcium released on uptake of the melanosome? Does it arise from Ca2+ stores within the keratinocyte, or, given the ability of melanin to bind calcium as described in a recent paper in this journal from the John Simon lab, is it released from within the transferred melansome? And second, what is the role of the released Ca2+? One possibility is that it primes the keratinocyte to mobilise its intra-cellular transport machinery to correctly position the incoming melansome. Alternatively, the calcium release detected by Joshi et al could potentially be a component of the hypothesized feedback mechanism by which keratinocytes would tell melanocytes that a melanosome has been received. Whatever the answers to these questions, monitoring Ca2+ release within keratinocytes will represent a useful tool to those wishing to identify the mechanism underlying melanosome transfer. The close contact between melanocytes and keratinocytes underpins melanosome transfer, but the ability of melanocytes and keratinocytes to stick together has become a focus of research on vitiligo, a complex disease characterised by loss of epidermal and follicular melanocytes. Several models have been proposed to explain the various features of melanocytes, many of which are covered in the reviews on vitiligo genetics by Rich Spritz in the last issue of Pigment Cell Research and in the review from Westerhof and d’Ischia in this issue. It is clear that one feature of melanocyte loss in vitiligo is their destruction by an auto-immune response. Precisely what triggers the auto-immunity isn’t well defined, but both Westerhof and d’Ischia, as well as Namazi, provide a number of suggestions based on the possibility that modification of melanocyte proteins would lead to the production of neo-antigens not normally encountered by the immune system. The presence of neo-antigens would then lead to a bystander effect and the potential for an auto-immune based reaction against melanocytes. However, for neo-antigens to be seen by the immune system would require their release from within melanocytes. Here, accumulating evidence suggest that the melanocytes from vitiligo prone individuals may be more sensitive to stress. In other words, the threshold for stress-induced damage to melanocytes in vitiligo patients would be substantially lower than in normal individuals. One way in which stress might affect melanocytes is in their ability to interact with surrounding keratinocytes, and indeed stress signalling is known to down-regulate the key cell–cell adhesion molecule E-cadherin. In the paper from Cario-André et al., the response of melanocytes in skin reconstructs to various stressors is examined. In agreement with the stress-sensitivity hypothesis, the melanocytes derived from non-lesional skin from individuals with vitiligo behaved differently from melanocytes from non-affected individuals. The defects were enhanced if the melanocytes from vitiligo individuals were combined with keratinocytes from non-lesional skin. The results presented, suggest that there may well be a degree of systemic stress-hypersensitivity in the epidermal melanocyte–keratinocyte interactions in individuals with vitiligo.

Constitutive Expression of B7-1 on B Cells Uncovers Autoimmunity toward the B Cell Compartment in the Nonobese Diabetic Mouse

The NOD mouse is an invaluable model for the study of autoimmune diabetes. Furthermore, although less appreciated, NOD mice are susceptible to other autoimmune diseases that can be differentially manifested by altering the balance of T cell costimulatory pathways. In this study, we show that constitutively expressing B7-1 on B cells (NOD-B7-1B-transgenic mice) resulted in reduced insulitis and completely protected NOD mice from developing diabetes. Furthermore, B7-1 expression led to a dramatic reduction of the B cell compartment due to a selective deletion of follicular B cells in the spleen, whereas marginal zone B cells were largely unaffected. B cell depletion was dependent on B cell specificity, mediated by CD8(+) T cells, and occurred exclusively in the autoimmune-prone NOD background. Our results suggest that B cell deletion was a consequence of the specific activation of autoreactive T cells directed at peripheral self Ags presented by maturing B cells that expressed B7-1 costimulatory molecules. This study underscores the importance of B7 costimulatory molecules in controlling the amplitude and target of autoimmunity in genetically prone individuals and has important implications in the use of costimulatory pathway antagonists in the treatment of human autoimmune diseases.

Prevention of Ischemic Stroke: Antithrombotic Therapy in Cardiac Embolism

Ischemic stroke secondary to cardiac disease accounts for approximately 30% of all stroke subtypes and it may be due to a large list of conditions. Stroke secondary to heart disease causes more severe deficits, higher mortality, and increased costs that other stroke subtypes. Therefore, proper identification of cardioembolic stroke is crucial for adequate selection of optimal preventive strategies. Identification of stroke prone individuals with heart disease could also have an important therapeutic impact. This manuscript reviews the interaction between the heart and brain with a particularly emphasis in the current state of older and newer antithrombotic drugs for stroke prevention in patients with atrial fibrillation. Other neuro-cardiological issues reviewed include current antithrombotic strategies in patients with a host of heart conditions which include pacemakers, acute myocardial infarction, congestive heart failure, cardiac procedures, patent foramen ovale, valve disease, endocarditis, or cardiac tumours.

Gut Involvement in NOD Mouse Diabetes

The non obese diabetic (NOD) mouse is a very well studied model of autoimmune diabetes. NOD mice develop insulitis, an early infiltration of leukocytes into the pancreas that leads to inflammatory lesions within the islets. In NOD mice, it has been shown that diet modifies the incidence of the disease. In particular, the diabetogenic agents come from the plant protein fraction of the natural food; cereal and soy bean proteins remain the major identified diabetogenic food components. More recently, it was shown that the gluten-free diet both delayed and prevented diabetes onset in NOD mice that had never been exposed to gluten. Compelling evidences of gut immune system involvement in diabetes is also provided by this model. Lymphocytes expressing mucosal adhesion molecules have been found to infiltrate the islets, while MadCAM blockage inhibits the development of diabetes; furthermore, diabetes has been shown to be transferred with mesenteric lymph nodes cells, at the age of 3 months the most diabetogenic cells being in the GALT (Gut Associated Lymphoid Tissue). Mice fed wheat containing diet have not only a higher incidence of diabetes, but also signs of small intestinal enteropathy and higher mucosal levels of proinflammatory cytokines. They show significant levels of serum antitTG antibodies, and single-chain antibody fragments to mouse tTG have been isolated mainly from the antibody libraries made from intestinal lymphocytes. While there is little doubt about the involvement of the intestinal immune response in the pathogenesis of diabetes, it is still unclear if dietary proteins (e.g. wheat) primarily trigger the inflammatory and then the autoimmune process in genetically prone individuals. Alternatively, dietary proteins could act on an already inflamed mucosa, because structurally more leaky or because the site of an ongoing autoimmune process, causing further damage. Keywords: NOD mouse, enteropathy, cytokines, gluten, diabetes, coeliac disease

Interactions between the “cognitive” and “metabolic” brain in the control of food intake

If the new environment and modern lifestyle cause obesity in individuals with thrifty genes by increasing energy intake, it is important to know by what mechanisms hyperphagia occurs and why energy balance is not kept in check by the homeostatic regulator. The argument is developed that procuring and ingesting food is an evolutionarily conserved survival mechanism that occupies large parts of the brain's computing capacity including not only the hypothalamus but also a number of cortico-limbic structures. These forebrain systems evolved to engage powerful emotions for guaranteed supply and ingestion of beneficial foods from a sparse and often hostile environment. They are now simply overwhelmed with an abundance of food and food cues that is no longer interrupted by frequent famines. After briefly reviewing structure and functions of the relevant cortico-limbic structures and the better-known hypothalamic homeostatic regulator, the review focuses mainly on interactions between the two systems. Although several cortico-limbic processes are sensitive to metabolic depletion and repletion signals, it appears that they are underlying the same reversible leptin resistance that renders hypothalamic circuits insensible to continuously high leptin levels during periods of feast. It is hypothesized that this naturally occurring leptin resistance allowed temporary neutralization of satiety mechanisms and evolved as a response to survive subsequent periods of famine. With today's continuous and abundant food availability for a segment of the population, the powerful cognitive processes to eat and the resulting overweight can partially escape negative feedback control in prone individuals most strongly expressing such thrifty genes.

Jumping to conclusions and the continuum of delusional beliefs

The present study examined the jumping to conclusions reasoning bias across the continuum of delusional ideation by investigating individuals with active delusions, delusion prone individuals, and non-delusion prone individuals. Neutral and highly self-referent probabilistic reasoning tasks were employed. Results indicated that individuals with delusions gathered significantly less information than delusion prone and non-delusion prone participants on both the neutral and self-referent tasks, ( p<.001). Individuals with delusions made less accurate decisions than the delusion prone and non-delusion prone participants on both tasks ( p<.001), yet were more confident about their decisions than were delusion prone and non-delusion prone participants on the self-referent task ( p=.002). Those with delusions and those who were delusion prone reported higher confidence in their performance on the self-referent task than they did the neutral task ( p=.02), indicating that high self-reference impacted information processing for individuals in both of these groups. The results are discussed in relation to previous research in the area of probabilistic reasoning and delusions.

Effect of Varying Doses of Aspirin on Blood Coagulation Variables After Cold Exposure in Healthy Males

INTRODUCTION: Previous research has elucidated that blood coagulation factors are a contributing factor in the incidence of cardiovascular disease (CVD). Aspirin is often prescribed as it is a common medication that may serve as an anti-coagulant. Research has demonstrated that the four to six hours following acute cold exposure (ACE) appears to be a critical time in coronary prone individuals whereby there is an increased risk for a cardiac event due to alterations in blood coagulation. Therefore, it is uncertain whether the individual who has been fed varying doses of aspirin for one week prior to cold exposure is able to decrease the risk of clot formation. PURPOSE: To determine the effect of different doses of aspirin vs. placebo (PLA) during a two hour recovery from exposure to 120C cold air. METHODS: Seven males (26.1+2.4 y) underwent pre-experimental testing to determine VO2max and body composition. Subjects underwent 3 trials in which they were required to ingest for one week prior to all trials: a capsule which was filled with cellulose (PLA), 81 mg.day-1 of aspirin (ASA-L), and 650 mg.day-1 of aspirin (ASA-H). Each trial consisted of 120 min of exposure to 12oC air and 120 min of recovery in 25oC air. Blood samples were obtained at 0, 60, and 120-minutes and analyzed for blood coagulation markers and clotting times. RESULTS: ANOVA revealed a main effect for treatment for prothrombin time (p < 0.001) and fibrinogen levels (p = 0.025), with low-dose aspirin demonstrating slower clotting times and lower levels of fibrinogen. In addition, there was a treatment x time interaction for prothrombin time (p < 0.001). CONCLUSION:Based on these data, the lower dose of aspirin slowed clotting time and decreased fibrinogen levels which may therefore contribute to a decrease in coagulation during the recovery period following ACE.

Using the Anger Response Inventory to Evaluate the Effect of Shame and Guilt on Interpersonal Communication Skills

Promoting the development of positive interpersonal communication skills has been identified as one of the National Health Education Standards. The propensity to feel shame has been linked to ineffective conflict resolution and is a key component in the development of certain destructive behavioral patterns. This study sought to determine the differences between shame proneness and guilt proneness on measures of constructive and maladaptive responses to anger among a population of students at two large universities. The results of this study indicated that shame proneness was positively correlated with anger arousal, whereas there was no correlation between guilt proneness and anger arousal. Additionally, shame prone individuals were more likely to select maladaptive, nonconstructive interpersonal responses to anger-eliciting scenarios, whereas guilt prone individuals were more likely to choose adaptive, constructive responses. Although shame proneness has been identified as a factor in several destructive behavioral patterns, the core issue is the effect of shame on a person's ability to effectively communicate in interpersonal relationships. A discussion of shame and related skill development could be incorporated into existing interpersonal communication teaching strategies.

Does the Perceived Risk of Punishment Deter Criminally Prone Individuals? Rational Choice, Self-Control, and Crime

Society’s efforts to deter crime with punishment may be ineffective because those individuals most prone to commit crime often act impulsively, with little thought for the future, and so they may be unmoved by the threat of later punishment. Deterrence messages they receive, therefore, may fall on deaf ears. This article examines this issue by testing the relationship between criminal propensity, perceived risks and costs of punishment, and criminal behavior. The authors analyzed data from the Dunedin (New Zealand) Study, a longitudinal study of individuals from birth through age26(N = 1,002). They found that in fact, deterrence perceptions had their greatest impact on criminally prone study members.

Transient modification of baroreceptor response during tilt-induced vasovagal syncope.

Normally, arterial baroreceptors attempt to minimize systemic hypotension by initiating reflex vasoconstriction and tachycardia. However, in the setting of vasovagal syncope (VVS), these usual compensatory mechanisms either fail to be triggered or the response is inadequate. We hypothesized that in VVS prone individuals, arterial baroreceptor response (BRR) is normal under most conditions, but that a transient functional BRR disturbance occurs during an evolving vasovagal faint and may in part account for failure of the usual compensatory response. This study assessed BRR in the baseline state and again in association with either VVS induced head-up tilt (HUT) or after a prolonged period of upright posture without VVS. To minimize impact on HUT outcome, BRR was estimated non-pharmacologically by measuring blood pressure and heart rate changes, induced when subjects were returned to the supine position after undergoing diagnostic 70 degrees HUT evaluation. Beat to beat heart rate and arterial blood pressure changes were recorded in 13 patients with syncope and another 16 individuals with negative HUT (control group). Baseline BRR was initially evaluated at the end of a 3 min symptom free HUT (HUT#1), and the measurement was repeated after a 45 min duration HUT in the control group or in conjunction with syncope in VVS prone individuals (HUT#2). Baseline BRR did not differ significantly in controls and VVS prone individuals (controls: 3.37+/-1.56, VVS prone: 6.0+/-2.02 ms/mmHg, p=0.27). Further, at the end of 45 min HUT#2, BRR was unaltered from baseline in control subjects (4.92+/-1.36 ms/mmHg, p=0.48), but was markedly reduced from baseline value in individuals who experienced a faint, -3.30+/-0.81 ms/mmHg (p<0.0003 vs baseline). Compared with individuals who do not manifest VVS during HUT, VVS prone individuals appear to demonstrate functional diminution of baroreceptor responsiveness. This altered response may undermine the normal expected compensatory response to evolving systemic hypotension. The basis for this transient disturbance in baroreceptor responsiveness is currently unknown.

Stress Exposure, Race, and Young Adult Male Crime

A recent revision of strain theory, Robert Agnew's (1992) general strain theory (GST), has stimulated research testing its principles, central of which is the notion that exposure to stressors is positively associated with criminal behavior. The present research extends prior scholarship in three important ways: (1) assessing the role that race and ethnicity play in understanding the stress-crime relationship, (2) testing GST principles on an underexamined group of crime prone individuals (i.e., young adults), and (3) examining the stress-crime association with a substantially more comprehensive set of measures of stressors than prior evaluations. Central to our findings is the result that racial differences in criminal involvement are largely reducible to exposure differences, with blacks typically exposed to significantly more stressful events over their lifetimes than members of other racial/ethnic groups.

Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients

Purpose : To investigate whether transforming growth factor beta-1 (TGF β1) single nucleotide polymorphisms were associated with the susceptibility of breast cancer patients to severe radiationinduced normal tissue damage. Materials and methods : PCR-RFLP assays were performed for TGF β1 gene polymorphisms on DNA obtained from 103 breast cancer patients who received radiotherapy. The G −800A, C −509T, T+869C and G+915C polymorphic sites were examined, and genotype and allele frequencies of two subgroups of patients were calculated and compared. Results : The less prevalent −509T and +869C alleles were significantly associated with a subgroup of patients who developed severe radiation-induced normal tissue fibrosis (n =15) when compared with those who did not (n =88) (odds ratio=3.4, p =0.0036, and 2.37, p =0.035, respectively). Furthermore, patients with the −509TT or +869CC genotypes were between seven and 15 times more likely to develop severe fibrosis. Conclusions : These findings imply a role for the −509T and +869C alleles in the pathobiological mechanisms underlying susceptibility to radiation-induced fibrosis. Their predictive value would be limited to patients who are −509TT or +869CC, but if 'fibrosis-associated' polymorphic sites in other genes could be identified, it may be possible to detect fibrosis prone individuals before radiotherapy with greater certainty.

Alternative treatment of gallbladder disease

Major risk factors for gallbladder disease include a sedentary lifestyle and a diet rich in refined sugars. In genetically prone individuals, these two factors lead to an abnormal bile composition, altered gut microflora, and hyperinsulinemia, with resulting gallstone formation. As a large percentage of gallbladder patients have continued digestive complaints following cholecystectomy, the author examines complementary and alternative medicine (CAM) treatments to counteract gallstone formation. Herbal medicine such as turmeric, oregon grape, bupleurum, and coin grass may reduce gallbladder inflammation and relieve liver congestion. Elimination of offending foods, not necessarily ‘fatty’ foods, is often successful and recommended by many holistic physicians. Regular aerobic exercise has a beneficial effect on hyperinsulinemia, which is often associated with gallbladder disease. Dietary changes that lower plasma insulin levels, such as a change in dietary fats and substitution of unrefined carbohydrates for refined carbohydrates, may also be helpful.